Multi-modality imaging to determine the cellular heterogeneity of nasopharyngeal carcinoma components.

// Weidong Zhang 1,* , Yanling Zhang 2,* , Shi Ke 3 , Mingjian Lu 1,* , Guang Yang 1 , Tao Zhang 1 , Jianjun Han 1 , Zhenyin Liu 1 , Wei Wang 3 , Henry Ran 3 , Chaoxia Zou 3,4 , Shaofan Hu 5 , Guangtao Lei 6 , Chuanxing Li 1 , Fujun Zhang 1 1 State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China 2 School of Biotechnology, Southern Medical University, Tonghe, Guangzhou, Guangdong, 510515, P.R. China. 3 Department of Radiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA 4 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, 150081, P. R. China 5 Jiangxi Children’s Hospital, Nanchang, Jiangxi, 330006, P.R. China 6 Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, P.R. China * These authors contributed equally to this manuscript Correspondence: Fujun Zhang, email: // Chuanxing Li, email: // Keywords : CT, FDG, CXCR4, retinoid acid, MMP, molecular imaging, multi-agent imaging, multi-modality imaging, optical imaging, PET. Received : February 13, 2014 Accepted : April 11, 2014 Published : April 11, 2014 Abstract Nasopharyngeal carcinoma (NPC) is an endemic public health problem in South and Southeast Asian countries. The disease components at the molecular level are unclear and need exploration for the development of future individualized molecular medicine. The purpose of this study was to test the feasibility of target-specific agents to detect different components of NPC. The binding capability of human NPC cell lines was determined by incubation with either agents that specifically target the metabolic status, host cytokines, and stroma. Mice bearing human NPC xenografts were injected with the same test agents plus a clinical molecular imaging agent ( 18 F-fluorodeoxyglucose) and computer tomography (CT) contrast agent. In vitro cell studies have demonstrated that target-specific agents bind to NPC cells with significantly higher signal intensities. Those agents not only bound to the cell membrane but also penetrated into the cytosol and cell nuclei. In vivo imaging demonstrated that the human NPC xenografts revealed high glucose uptake and a profound vasculature in the tumor. All agents were bound to the tumor regions with a high tumor-to-muscle ratio. Finally, all imaging data were validated by histopathological results. Multiple, target-specific agents determine the dynamic and heterogeneous components of NPC at the molecular level.